Global Patent Index - EP 2177503 A1

EP 2177503 A1 20100421 - MODULATORS OF CANNABINOID RECEPTORS

Title (en)

MODULATORS OF CANNABINOID RECEPTORS

Title (de)

CANNABINOID-REZEPTORMODULATOREN

Title (fr)

MODULATEURS DES RÉCEPTEURS CANNABINOÏDES

Publication

EP 2177503 A1 20100421 (EN)

Application

EP 09012361 A 20050221

Priority

  • EP 05708399 A 20050221
  • GB 0403864 A 20040220

Abstract (en)

The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt thereof, wherein Z is OR 1 or NR 1 R 2 wherein each of R 1 and R 2 is independently H, or a hydrocarbyl group;X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO 2 -alkyl, alkenyl, CN, NH 2 , hydroxy, halo, alkoxy, CF 3 and nitro; Y is a polar functional group selected from OH, NO 2 CN, COR 3 , COOR 3 , NR 3 R 4 , CONR 3 R 4 , SO 3 H, SO 2 -R 3 , SO 2 NR 3 R 4 and CF 3 , where each of R 3 and R 4 is independently H or a hydrocarbyl group; A is an aryl or heteroaryl group, each of which may be optionally substituted; and B is (CH 2 ) n where n is 0, 1, 2, 3, 4 or 5; with the proviso that: (i) when A is phenyl, n is 0, and Z is OH, X-Y is other than meta -C‰¡C-(CH 2 ) 2 CO 2 H, meta -C‰¡C-(CH 2 ) 2 OH, meta -C‰¡C-(CH 2 ) 2 CO 2 Me, meta- (CH 2 ) 4 CO 2 H, ortho -CH 2 CO 2 H, ortho -(CH 2 ) 2 CO 2 H and ortho -(CH 2 ) 4 CO 2 H; and (ii) when A is phenyl, n is 0, and Z is OMe, X-Y is other than meta -C‰¡C-(CH 2 ) 4 OH. Further aspects of the invention relate to the use of such compounds in the preparation of a medicament for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors.

IPC 8 full level

C07C 233/68 (2006.01); A61K 31/167 (2006.01); A61K 31/192 (2006.01); A61K 31/216 (2006.01); A61K 31/235 (2006.01); C07C 63/04 (2006.01); C07C 69/76 (2006.01); C07C 69/78 (2006.01); C07C 233/11 (2006.01); C07C 233/65 (2006.01); C07C 233/66 (2006.01); C07C 233/69 (2006.01); C07C 233/77 (2006.01); C07C 235/42 (2006.01); C07C 235/78 (2006.01); C07C 235/84 (2006.01); C07C 237/32 (2006.01); C07C 237/38 (2006.01); C07C 237/42 (2006.01); C07C 255/41 (2006.01)

CPC (source: EP NO US)

A61K 31/165 (2013.01 - US); A61K 31/167 (2013.01 - NO); A61P 1/00 (2018.01 - EP); A61P 1/04 (2018.01 - EP); A61P 1/12 (2018.01 - EP); A61P 13/10 (2018.01 - EP); A61P 21/00 (2018.01 - EP); A61P 21/02 (2018.01 - EP); A61P 25/00 (2018.01 - EP); A61P 25/28 (2018.01 - EP); A61P 37/02 (2018.01 - EP); A61P 43/00 (2018.01 - EP); C07C 69/76 (2013.01 - EP US); C07C 69/78 (2013.01 - NO US); C07C 233/11 (2013.01 - EP US); C07C 233/65 (2013.01 - EP US); C07C 233/66 (2013.01 - EP US); C07C 233/68 (2013.01 - NO); C07C 233/69 (2013.01 - EP US); C07C 233/77 (2013.01 - NO); C07C 235/34 (2013.01 - US); C07C 235/42 (2013.01 - EP US); C07C 235/78 (2013.01 - EP US); C07C 235/84 (2013.01 - EP US); C07C 237/32 (2013.01 - EP US); C07C 237/38 (2013.01 - EP US); C07C 237/42 (2013.01 - EP US); C07C 255/41 (2013.01 - EP US); C07C 255/44 (2013.01 - US)

Citation (applicant)

  • US 5874459 A 19990223 - MAKRIYANNIS ALEXANDROS [US], et al
  • WO 8403564 A1 19840913 - COMMW SERUM LAB COMMISSION [AU]
  • US 3817837 A 19740618 - RUBENSTEIN K, et al
  • US 3850752 A 19741126 - SCHUURS A, et al
  • US 3939350 A 19760217 - KRONICK MELVYN N, et al
  • US 3996345 A 19761207 - ULLMAN EDWIN F, et al
  • US 4277437 A 19810707 - MAGGIO EDWARD T
  • US 4275149 A 19810623 - LITMAN DAVID J, et al
  • US 4366241 A 19821228 - TOM HENRY K, et al
  • EP 0184438 A2 19860611 - ALLELIX INC [CA]
  • EP 0284603 A1 19881005 - ALLELIX INC [CA]
  • EP 0134048 A1 19850313 - GIST BROCADES NV [NL]
  • EP 0253455 A1 19880120 - GIST BROCADES NV [NL]
  • EP 0096430 A1 19831221 - GIST BROCADES NV [NL]
  • EP 0301670 A1 19890201 - GIST BROCADES NV [NL]
  • EP 0449375 A2 19911002 - GIST BROCADES NV [NL], et al
  • BAKER, D. ET AL., NATURE, vol. 404, 2000, pages 84 - 87
  • BAKER, D. ET AL., FASEB J., vol. 15, 2001, pages 300 - 302
  • SCHNELTE, M. ET AL., FORSCH. KOMPLEMENTARMED, vol. 6, no. 3, 1999, pages 28 - 36
  • PERTWEE, R. G., PHARMACOLOGY & THERAPEUTICS, vol. 74, 1997, pages 129 - 180
  • BERGLUND, B. A. ET AL., DRUG DESIGN AND DISCOVERY, vol. 16, 2000, pages 281 - 294
  • PERTWEE, R. G., PROG. NEUROBIOL., vol. 63, 2001, pages 569 - 611
  • HERZBERG, U. ET AL., NEUROSCI. LETT., vol. 221, 1997, pages 157 - 160
  • RICHARDSON, J. D., PAIN, vol. 75, 1998, pages 111 - 119
  • IAGGAR, S. I. ET AL., PAIN, vol. 76, 1998, pages 189 - 199
  • CALIGNANO, A. ET AL., NATURE, vol. 394, 1998, pages 277 - 281
  • HANUS, L. ET AL., PROC. NATL. ACAD. SCI. U. S. A, vol. 96, 1999, pages 14228 - 14233
  • HOWLETT, A. C. ET AL.: "International Union of Pharmacology XXVII", PHARMACOL. REV., vol. 54, 2002, pages 161 - 202
  • PERTWEE, R. G.: "Pharmacology of cannabinoid receptor ligands", CURR. MED. CHEM., vol. 6, 1999, pages 635 - 664
  • KREITZER, A. C. ET AL., NEURON, vol. 29, 2001, pages 717 - 727
  • WILSON, R. I. ET AL., NEURON, vol. 31, 2001, pages 453 - 462
  • HOWLETT, A. C., NEUROBIOL. DIS., vol. 5, 1998, pages 405 - 416
  • PERTWEE, R. G., LIFE SCI., vol. 65, 1999, pages 597 - 605
  • FOX, A. ET AL., PAIN, vol. 92, 2001, pages 91 - 100
  • TAMAI, I. ET AL., J. PHARM. SCI., vol. 89, 2000, pages 1371 - 1388
  • WANDEL, C. ET AL., ANESTHESIOLOGY, vol. 96, 2002, pages 913 - 920
  • SEELIG, A. ET AL., EUR. J. PHARM. SCI., vol. 12, 2000, pages 31 - 40
  • DI MARZO, BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1392, 1998, pages 153 - 175
  • PERTWEE, PHARMACOL THER, vol. 74, 1997, pages 129 - 180
  • MATSUDA ET AL., NATURE, vol. 346, 1990, pages 561 - 564
  • MODI; BONNER, CYTOGENET. CELL GENET., vol. 58, 1991, pages 1915
  • GERARD ET AL., BIOCHEM. J, vol. 279, 1991, pages 129 - 134
  • HOEHE ET AL., NEW BIOLOGIST, vol. 3, 1991, pages 880 - 885
  • LEDENT ET AL., SCIENCE, vol. 28-3, 1999, pages 401 - 404
  • MUNRO, NATURE, vol. 365, 1993, pages 61 - 65
  • HOYE, R. C. ET AL., L ORG. CHEM., vol. 64, 1999, pages 2450 - 2453
  • HOPPER, A. T. ET AL., J. MED. CHEM., vol. 41, 1998, pages 420 - 427
  • BUTTER, C. ET AL., J. NEUROL. SCI., vol. 104, 1991, pages 9 - 12
  • DANIEL, P. M. ET AL., J. NEUROL. SCI., vol. 60, 1983, pages 367 - 376
  • JUHLER, M. ET AL., BRAIN RES., vol. 302, 1984, pages 347 - 355
  • IZZO, A. A. ET AL., BR. J. PHARMACOL., vol. 129, 2000, pages 1627 - 1632
  • LANDI, M. ET AL., EUR. J. PHARMACOL., vol. 450, 2002, pages 77 - 83
  • PINTO, L. ET AL., GASTROENTEROLOGY, vol. 123, 2002, pages 227 - 234
  • "Handbook of Pharmaceutical Excipients", 1994
  • "Remington's Pharmaceutical Sciences", 1985, MACK PUBLISHING CO.
  • BERGE ET AL., J PHARM SCI, vol. 66, 1977, pages 1 - 19
  • HAMPTON R ET AL.: "Serological Methods, A Laboratory Manual", 1990, APS PRESS
  • MADDOX DE ET AL., J EXP MED, vol. 15 8, 1983, pages 121 1
  • PETROCELLIS ET AL., FEBS LETTER, vol. 483, 2000, pages 52 - 56
  • SAMBROOK ET AL.: "Molecular Cloning: A Laboratory Manual", 1989, COLD SPRING HARBOR LABORATORY PRESS
  • AUSUBEL ET AL.: "Current Protocols in Molecular Biology", 1995, JOHN WILEY & SONS, INC
  • GOODEY ET AL.: "Yeast Biotechnology", 1987, ALLEN AND UNWIN, pages: 401 - 429
  • KING ET AL.: "Molecular and Cell Biology of Yeasts", 1989, BLACKIE, GLASGOW, pages: 107 - 133
  • E HINCHCLIFFE; E KENNY: "Yeasts", vol. 5, 1993, ACADEMIC PRESS LTD., article "Yeast as a vehicle for the expression of heterologous genes"
  • HINNEN ET AL., PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE USA, vol. 75, 1978, pages 1929
  • BEGGS, J D, NATURE, vol. 275, 1978, pages 104
  • ITO, H ET AL., J BACTERIOLOGY, vol. 153, 1983, pages 163 - 168
  • POTRYKUS, ANNU REV PLANT PHYSIOL PLANT MOL BIOL, vol. 42, 1991, pages 205 - 225
  • CHRISTOU, AGRO-FOOD-INDUSTRY HI-TECH, March 1994 (1994-03-01), pages 17 - 27
  • KROLL DJ ET AL., DNA CELL BIOL, vol. 12, 1993, pages 441 - 53
  • DRUG DESIGN AND DISCOVERY, 2000, pages 281 - 294
  • TETRAHEDRON, vol. 56, 2000, pages 4777 - 4792
  • J. ORG. CHEM., vol. 64, 1999, pages 4777 - 4792
  • J MED. CHEM., vol. 41, 1998, pages 420 - 427
  • ROSS, R. A. ET AL., BR. J. PHARMACOL., vol. 128, 1999, pages 735 - 743
  • CHENG, Y.; PRUSOFF, W. H., BIOCHEM. PHARMACOL., vol. 22, 1973, pages 3099 - 3108
  • WARD S ET AL., J PHARMACOL EXP THER, vol. 255, 1990, pages 1230 - 1239
  • PINTO ET AL., GASTROENTEROLOGY, vol. 123, 2002, pages 227 - 234
  • HOWLETT, A. C. ET AL.: "International Union of Pharmacology. XXVII", PHARMACOL. REV., vol. 54, 2002, pages 161 - 202
  • BROOKS, J. W. ET AL., EUR. J. PHARMACOL., vol. 439, 2002, pages 83 - 92
  • OHNO, K. ET AL., AM. J. PHYSIOL, vol. 235, 1978, pages H299 - H307
  • ZHOU, L. ET AL., FEBS LETT., vol. 523, 2002, pages 68 - 72
  • AMOR, S. ET AL., J. IMMUNOL., vol. 153, 1994, pages 4349 - 4356
  • BAKER, D. ET AL., J. NEUROIMMUNOL., vol. 28, 1990, pages 261 - 270
  • BAKER, D. ET AL., NATURE, vol. 404, 2000, pages 84 - 87
  • ZHOU, L. ET AL., FEBS LETT., vol. 523, 2002, pages 68 - 72
  • AMOR, S. ET AL., J, IMMUNOL., vol. 153, 1994, pages 4349 - 4356
  • BAKER, D. ET AL., NEUROIMMUNOL., vol. 28, 1990, pages 261 - 270

Citation (search report)

  • [PX] WO 2004078180 A2 20040916 - GUILFORD PHARM INC [US], et al
  • [PXPY] WO 2004024939 A2 20040325 - UNIV GEORGETOWN [US], et al & DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; KOZIKOWSKI, ALAN P. ET AL: "Ligands for the peroxisome proliferator-activated receptor", retrieved from STN Database accession no. 140:287710
  • [Y] WO 0016756 A2 20000330 - INNOVET ITALIA SRL [IT], et al
  • [Y] US 5342971 A 19940830 - HERLT TONY JOHN [AU], et al
  • [Y] US 2003191069 A1 20031009 - INABA TAKASHI [JP], et al
  • [XY] WO 03040096 A2 20030515 - ELAN PHARM INC [US], et al & DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; VARGHESE, JOHN ET AL: "Preparation of N,N'-substituted-1,3-diamino-2-hydroxypropanes for treating Alzheimer's disease", retrieved from STN Database accession no. 138:385173
  • [X] US 4948796 A 19900814 - HIRAIWA TORU [JP], et al
  • [X] EP 0329464 A2 19890823 - GENSIA PHARMA [US] & DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TUTTLE, RONALD RALPH ET AL: "Diagnosis, evaluation, and treatment of coronary artery disease by exercise simulation using closed-loop drug delivery of an exercise-simulating catecholamine .beta.-agonist", retrieved from STN Database accession no. 114:602
  • [X] EP 0146920 A2 19850703 - KEY PHARMA [US] & DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TUTTLE, RONALD R.: "Orally effective inotropic compounds", retrieved from STN Database accession no. 104:5650
  • [XY] DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TAKADO, TORU ET AL: "Novel imidazoquinolinones and their use as antiparkinsonian agents", XP002555427, retrieved from STN Database accession no. 140:210794 & JP 2004059538 A 20040226 - SUMITOMO PHARMA
  • [X] DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TAKESHITA, HIROSHI ET AL: "Polymerizable unsaturated group-containing N-substituted amides for bisphenol A-free dental materials", XP002555428, retrieved from STN Database accession no. 133:125328 & JP 2000204069 A 20000725 - TOKUYAMA CORP
  • [X] DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; MCDOWELL, ROBERT S. ET AL: "From Peptide to Non-Peptide. 2. The de Novo Design of Potent, Non-peptidal Inhibitors of Platelet Aggregation Based on a Benzodiazepinedione Scaffold", XP002555429, retrieved from STN Database accession no. 121:99058 & JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 116(12), 5077-83 CODEN: JACSAT; ISSN: 0002-7863, 1994, XP002555501
  • [X] DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; CALDWELL, ROBERT W. ET AL: "Cardiovascular effects of KM-13, a new, orally effective, cardiotonic sympathomimetic amine", XP002555430, retrieved from STN Database accession no. 106:207185 & JOURNAL OF CARDIOVASCULAR PHARMACOLOGY , 9(3), 375-84 CODEN: JCPCDT; ISSN: 0160-2446, 1987, XP002555502
  • [X] DATABASE BEILSTEIN [online] BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002555432, Database accession no. 7777227 (BRN) & VARNEY, M.PALMER, C. ET AL.: "Protein Structure - Based Design, Synthesis, and Biological Evaluation of 5-Thia-2,6-diamino-4(3H)-oxopyrimides: potent Inhibitors of Glycinamide Ribonucleotide Transformylase with Potent Cell Growth Inhibition", JOURNAL OF MEDICINAL CHEMISTRY, vol. 40, no. 16, 1997, pages 2502 - 2524, XP002555503
  • [X] DATABASE BEILSTEIN [online] BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002555433, Database accession no. 6932805 (BRN) & MCDOWELL, R.; BLACK B. ET AL., JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 116, no. 12, 1994, pages 5077 - 5083
  • [X] DATABASE BEILSTEIN [online] BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002555434, Database accession no. 6930766 (BRN) & MCDOWER.; B. ET AL., JOURNAL OF AMERICAN CHEMICAL SOCIETY, vol. 116, no. 12, 1994, pages 5077 - 5083
  • [X] DATABASE BEILSTEIN [online] BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002555435, Database accession no. 7776039 (BRN) & VARNEY, M; PALMER, C. ET AL., JOURNAL OF MEDICINAL CHEMISTRUY, vol. 40, no. 16, 1997, pages 2502 - 2542

Designated contracting state (EPC)

AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR

DOCDB simple family (publication)

WO 2005080316 A2 20050901; WO 2005080316 A3 20051103; AT E444279 T1 20091015; AU 2005214146 A1 20050901; AU 2005214146 B2 20120223; AU 2005214146 C1 20120920; BR PI0507914 A 20070710; BR PI0507914 A8 20160426; BR PI0507914 A8 20160510; BR PI0507914 A8 20160524; CA 2556940 A1 20050901; CA 2556940 C 20131210; CN 1956946 A 20070502; CN 1956946 B 20130710; CY 1115388 T1 20170104; DE 602005016915 D1 20091112; DK 2177503 T3 20130708; EP 1745011 A2 20070124; EP 1745011 B1 20090930; EP 2177503 A1 20100421; EP 2177503 B1 20130410; ES 2334365 T3 20100309; ES 2420115 T3 20130822; GB 0403864 D0 20040324; HK 1100079 A1 20070907; IL 177558 A0 20061210; IL 177558 A 20121231; JP 2007523150 A 20070816; JP 4925834 B2 20120509; MX PA06009433 A 20070321; NO 20064227 L 20061116; NO 337839 B1 20160627; NZ 549257 A 20101126; PL 2177503 T3 20131031; PT 2177503 E 20130716; SI 2177503 T1 20130930; US 2008114062 A1 20080515; US 2010144876 A1 20100610; US 2013123356 A1 20130516; US 2016107984 A1 20160421; US 7696382 B2 20100413; US 8293796 B2 20121023; US 9120723 B2 20150901

DOCDB simple family (application)

GB 2005000605 W 20050221; AT 05708399 T 20050221; AU 2005214146 A 20050221; BR PI0507914 A 20050221; CA 2556940 A 20050221; CN 200580012480 A 20050221; CY 131100499 T 20130619; DE 602005016915 T 20050221; DK 09012361 T 20050221; EP 05708399 A 20050221; EP 09012361 A 20050221; ES 05708399 T 20050221; ES 09012361 T 20050221; GB 0403864 A 20040220; HK 07108010 A 20070724; IL 17755806 A 20060817; JP 2006553673 A 20050221; MX PA06009433 A 20050221; NO 20064227 A 20060919; NZ 54925705 A 20050221; PL 09012361 T 20050221; PT 09012361 T 20050221; SI 200531741 T 20050221; US 201213654942 A 20121018; US 201514809331 A 20150727; US 59006405 A 20050221; US 70781210 A 20100218